Homeostasis of dendritic cells in lymphoid organs is controlled by regulation of their precursors via a feedback loop

Blood ◽  
2009 ◽  
Vol 114 (20) ◽  
pp. 4411-4421 ◽  
Author(s):  
Kristin Hochweller ◽  
Tewfik Miloud ◽  
Jörg Striegler ◽  
Shalin Naik ◽  
Günter J. Hämmerling ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Mouse Model ◽  
Feedback Loop ◽  
Immune Cell ◽  
Feedback Regulation ◽  
Cell Types ◽  
Active Process ◽  
Differentiation Potential ◽  
Cell Compartments

Abstract Dendritic cells (DCs) are key coordinators of the immune response, governing the choice between tolerance and immunity. Despite their importance, the mechanisms controlling the size of the DC compartment are largely unknown. Using a mouse model allowing continuous DC depletion, we show that maintenance of DC numbers in spleen is an active process mediated by Flt3-L–dependent regulation of precursor differentiation into DCs, rather than by changes in proliferation of the differentiated DCs. In particular, the frequency and differentiation potential of intrasplenic DC precursors increased in response to reduced DC numbers. Levels of Flt3-L, a cytokine required for DC differentiation, increased in the blood after DC depletion and returned to normal levels once the DC compartment filled up again. Our data suggest a feedback regulation of DC homeostasis whereby reduction of the DC pool size promotes differentiation of their precursors, via increased Flt3-L availability. This mechanism is different to those known for other immune cell types, such as the B- and T-cell compartments, whereby lymphopenia induces proliferation of already differentiated lymphocytes.

scholarly journals Characterisation of secretome-based immune responses of human leukocytes infected with various Mycobacterium tuberculosis lineages

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11565
Author(s):  
Benjawan Kaewseekhao ◽  
Sittiruk Roytrakul ◽  
Yodying Yingchutrakul ◽  
Marut Laohaviroj ◽  
Kanin Salao ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
B Cells ◽  
Immune Responses ◽  
Antigen Processing ◽  
Immune Cell ◽  
Cell Types ◽  
Label Free ◽  
Related Proteins

Background Differences in immune responses against different lineages of Mycobacterium tuberculosis (Mtb), and by different types of immune cell, are still poorly understood. We aimed to compare the secretome-based immune responses among three Mtb lineages and among immune-cell types. The immune responses were also investigated during infection and when the bacilli had been eliminated from the immune cells. Methods Human primary leukocytes were infected with strains representing three lineages of Mtb (East-Asian, Indo-Oceanic and Euro-American). Label-free GeLC MS/MS proteomic analysis of secretomes was performed. The response of each immune-cell type was compared with the appropriate interactome database for each. Results The expression pattern of proteins secreted by Mtb-infected leukocytes differed among Mtb lineages. The ancestral lineage (IO lineage) had a greater ability to activate MMP14 (associated with leukocyte migration) than did the more recent lineages (EA and EuA). During infection, proteins secreted by macrophages, dendritic cells, neutrophils and B-cells were associated with cell proliferation. Following clearance of Mtb, proteins associated with interferon signaling were found in macrophages, dendritic cells and neutrophils: proteins associated with antigen processing were found in B-cells and regulatory T-cells. Expression of immune response-related proteins from many immune-cell types might be suppressed by Mtb infection. Our study has provided a better insight into the host-pathogen interaction and immune response against different Mtb lineages.

scholarly journals Identification of immune-based prostate cancer subtypes using mRNA expression

2020 ◽  
Author(s):  
Jukun Song ◽  
Song He ◽  
Wei Wang ◽  
Jiaming Su ◽  
Dongbo Yuan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Response ◽  
Immune Cells ◽  
Immune Cell ◽  
Molecular Classification ◽  
Cell Types ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Cell Subpopulation ◽  
Immune Cell Infiltration

Abstract Background Immune infiltration of Prostate cancer (PCa) was highly related to clinical outcomes. However, previous works failed to elucidate the diversity of different immune cell types that make up the function of the immune response system. The aim of the study was to uncover the composition of TIICs in PCa utilizing the CIBERSORT algorithm and further reveal the molecular characteristics of PCa subtypes. Method In the present work, we employed the CIBERSORT method to evaluate the relative proportions of immune cell profiling in PCa and adjacent samples, normal samples. We analyzed the correlation between immune cell infiltration and clinical information. The tumor-infiltrating immune cells of the TCGA PCa cohort were analyzed for the first time. The fractions of 22 immune cell types were imputed to determine the correlation between each immune cell subpopulation and clinical feature. Three types of molecular classification were identified via R-package of “CancerSubtypes”. The functional enrichment was analyzed in each subtype. The submap and TIDE algorithm were used to predict the clinical response to immune checkpoint blockade, and GDSC was employed to screen chemotherapeutic targets for the potential treatment of PCa. Results In current work, we utilized the CIBERSORT algorithm to assess the relative proportions of immune cell profiling in PCa and adjacent samples, normal samples. We investigated the correlation between immune cell infiltration and clinical data. The tumor-infiltrating immune cells in the TCGA PCa cohort were analyzed. The 22 immune cells were also calculated to determine the correlation between each immune cell subpopulation and survival and response to chemotherapy. Three types of molecular classification were identified. Each subtype has specific molecular and clinical characteristics. Meanwhile, Cluster I is defined as advanced PCa, and is more likely to respond to immunotherapy. Conclusions Our results demonstrated that differences in immune response may be important drivers of PCa progression and response to treatment. The deconvolution algorithm of gene expression microarray data by CIBERSOFT provides useful information about the immune cell composition of PCa patients. In addition, we have found a subtype of immunopositive PCa subtype and will help to explore the reasons for the poor effect of PCa on immunotherapy, and it is expected that immunotherapy will be used to guide the individualized management and treatment of PCa patients.

scholarly journals Nonneuronal Cholinergic System in Breast Tumors and Dendritic Cells: Does It Improve or Worsen the Response to Tumor?

2013 ◽  
Vol 2013 ◽  
pp. 1-12
Author(s):  
Marisa Vulcano ◽  
María Gabriela Lombardi ◽  
María Elena Sales
Keyword(s):  
Dendritic Cells ◽  
Cholinergic System ◽  
Parasympathetic Nervous System ◽  
Immune Cell ◽  
Breast Tumors ◽  
Cell Types ◽  
Cellular Functions ◽  
And Migration ◽  
And Function

Besides being the main neurotransmitter in the parasympathetic nervous system, acetylcholine (ACh) can act as a signaling molecule in nonneuronal tissues. For this reason, ACh and the enzymes that synthesize and degrade it (choline acetyltransferase and acetylcholinesterase) as well as muscarinic (mAChRs) and nicotinic receptors conform the non-neuronal cholinergic system (nNCS). It has been reported that nNCS regulates basal cellular functions including survival, proliferation, adhesion, and migration. Moreover, nNCS is broadly expressed in tumors and in different components of the immune system. In this review, we summarize the role of nNCS in tumors and in different immune cell types focusing on the expression and function of mAChRs in breast tumors and dendritic cells (DCs) and discussing the role of DCs in breast cancer.

scholarly journals Mathematical Modeling of Within-Host, Untreated, Cytomegalovirus Infection Dynamics after Allogeneic Transplantation

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2292
Author(s):  
Elizabeth R. Duke ◽  
Florencia A. T. Boshier ◽  
Michael Boeckh ◽  
Joshua T. Schiffer ◽  
E. Fabian Cardozo-Ojeda
Keyword(s):  
Mathematical Modeling ◽  
Immune Response ◽  
Target Cell ◽  
Hematopoietic Cell Transplantation ◽  
Viral Infections ◽  
Immune Cell ◽  
Controlled Trial ◽  
Antiviral Treatment ◽  
Serum Samples ◽  
Cell Compartments

Cytomegalovirus (CMV) causes significant morbidity and mortality in recipients of allogeneic hematopoietic cell transplantation (HCT). Whereas insights gained from mathematical modeling of other chronic viral infections such as HIV, hepatitis C, and herpes simplex virus-2 have aided in optimizing therapy, previous CMV modeling has been hindered by a lack of comprehensive quantitative PCR viral load data from untreated episodes of viremia in HCT recipients. We performed quantitative CMV DNA PCR on stored, frozen serum samples from the placebo group of participants in a historic randomized controlled trial of ganciclovir for the early treatment of CMV infection in bone marrow transplant recipients. We developed four main ordinary differential Equation mathematical models and used model selection theory to choose between 38 competing versions of these models. Models were fit using a population, nonlinear, mixed-effects approach. We found that CMV kinetics from untreated HCT recipients are highly variable. The models that recapitulated the observed patterns most parsimoniously included explicit, dynamic immune cell compartments and did not include dynamic target cell compartments, consistent with the large number of tissue and cell types that CMV infects. In addition, in our best-fitting models, viral clearance was extremely slow, suggesting severe impairment of the immune response after HCT. Parameters from our best model correlated well with participants’ clinical risk factors and outcomes from the trial, further validating our model. Our models suggest that CMV dynamics in HCT recipients are determined by host immune response rather than target cell limitation in the absence of antiviral treatment.

scholarly journals Exploring the Innate Immunological Response of an Alternative Nonhuman Primate Model of Infectious Disease; the Common Marmoset

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
M. Nelson ◽  
M. Loveday
Keyword(s):  
Infectious Disease ◽  
Immune Response ◽  
Nonhuman Primate ◽  
Immune Cell ◽  
Common Marmoset ◽  
Cell Types ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
The Common ◽  
Activation Status

The common marmoset (Callithrix jacchus) is increasingly being utilised as a nonhuman primate model for human disease, ranging from autoimmune to infectious disease. In order to fully exploit these models, meaningful comparison to the human host response is necessary. Commercially available reagents, primarily targeted to human cells, were utilised to assess the phenotype and activation status of key immune cell types and cytokines in naive and infected animals. Single cell suspensions of blood, spleen, and lung were examined. Generally, the phenotype of cells was comparable between humans and marmosets, with approximately 63% of all lymphocytes in the blood of marmosets being T cells, 25% B-cells, and 12% NK cells. The percentage of neutrophils in marmoset blood were more similar to human values than mouse values. Comparison of the activation status of cells following experimental systemic or inhalational infection exhibited different trends in different tissues, most obvious in cell types active in the innate immune response. This work significantly enhances the ability to understand the immune response in these animals and fortifies their use as models of infectious disease.

scholarly journals Herpes Simplex Virus Type-2 Paralyzes the Function of Monocyte-Derived Dendritic Cells

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 112 ◽  
Author(s):  
Linda Grosche ◽  
Petra Mühl-Zürbes ◽  
Barbara Ciblis ◽  
Adalbert Krawczyk ◽  
Christine Kuhnt ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex ◽  
Immune Cell ◽  
Cell Types ◽  
Receptor Expression ◽  
Negative Regulator ◽  
Antigen Delivery ◽  
Herpes Simplex Viruses ◽  
Β2 Integrin

Herpes simplex viruses not only infect a variety of different cell types, including dendritic cells (DCs), but also modulate important cellular functions in benefit of the virus. Given the relevance of directed immune cell migration during the initiation of potent antiviral immune responses, interference with DC migration constitutes a sophisticated strategy to hamper antiviral immunity. Notably, recent reports revealed that HSV-1 significantly inhibits DC migration in vitro. Thus, we aimed to investigate whether HSV-2 also modulates distinct hallmarks of DC biology. Here, we demonstrate that HSV-2 negatively interferes with chemokine-dependent in vitro migration capacity of mature DCs (mDCs). Interestingly, rather than mediating the reduction of the cognate chemokine receptor expression early during infection, HSV-2 rapidly induces β2 integrin (LFA-1)-mediated mDC adhesion and thereby blocks mDC migration. Mechanistically, HSV-2 triggers the proteasomal degradation of the negative regulator of β2 integrin activity, CYTIP, which causes the constitutive activation of LFA-1 and thus mDC adhesion. In conclusion, our data extend and strengthen recent findings reporting the reduction of mDC migration in the context of a herpesviral infection. We thus hypothesize that hampering antigen delivery to secondary lymphoid organs by inhibition of mDC migration is an evolutionary conserved strategy among distinct members of Herpesviridae.

scholarly journals A multipotent precursor in the thymus maps to the branching point of the T versus B lineage decision

2005 ◽  
Vol 202 (1) ◽  
pp. 21-31 ◽  
Author(s):  
Claudia Benz ◽  
Conrad C. Bleul
Keyword(s):  
Dendritic Cells ◽  
Fluorescent Protein ◽  
Single Cells ◽  
Cell Types ◽  
Differentiation Potential ◽  
Lineage Decision ◽  
Branching Point ◽  
B Lineage ◽  
Green Fluorescent

Hematopoietic precursors continuously colonize the thymus where they give rise mainly to T cells, but also to B and dendritic cells. The lineage relationship between these three cell types is unclear, and it remains to be determined if precursors in the thymus are multipotent, oligopotent, or lineage restricted. Resolution of this question necessitates the determination of the clonal differentiation potential of the most immature precursors in the thymus. Using a CC chemokine receptor 9–enhanced green fluorescent protein knock-in allele like a surface marker of unknown function, we identify a multipotent precursor present in bone marrow, blood, and thymus. Single cells of this precursor give rise to T, B, and dendritic cells. A more differentiated stage of this multipotent precursor in the thymus has lost the capacity to generate B but not T, dendritic, and myeloid cells. Thus, the newly identified precursor maps to the branching point of the T versus B lineage decision in the hematopoietic lineage hierarchy.

scholarly journals A Catalogus Immune Muris of the mouse immune responses to diverse pathogens

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Céline Barlier ◽  
Diego Barriales ◽  
Alexey Samosyuk ◽  
Sascha Jung ◽  
Srikanth Ravichandran ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Biomedical Applications ◽  
Immune Cell ◽  
Cell Types ◽  
Computational Method ◽  
Functional Responses ◽  
Macrophage Cell ◽  
Functional States

AbstractImmunomodulation strategies are crucial for several biomedical applications. However, the immune system is highly heterogeneous and its functional responses to infections remains elusive. Indeed, the characterization of immune response particularities to different pathogens is needed to identify immunomodulatory candidates. To address this issue, we compiled a comprehensive map of functional immune cell states of mouse in response to 12 pathogens. To create this atlas, we developed a single-cell-based computational method that partitions heterogeneous cell types into functionally distinct states and simultaneously identifies modules of functionally relevant genes characterizing them. We identified 295 functional states using 114 datasets of six immune cell types, creating a Catalogus Immune Muris. As a result, we found common as well as pathogen-specific functional states and experimentally characterized the function of an unknown macrophage cell state that modulates the response to Salmonella Typhimurium infection. Thus, we expect our Catalogus Immune Muris to be an important resource for studies aiming at discovering new immunomodulatory candidates.

scholarly journals Immune Response in Severe and Non-Severe Coronavirus Disease 2019 (COVID-19) Infection: A Mechanistic Landscape

2021 ◽  
Vol 12 ◽  
Author(s):  
Kavitha Mukund ◽  
Priya Nayak ◽  
Chethan Ashokkumar ◽  
Sohail Rao ◽  
Jose Almeda ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cell ◽  
Severe Disease ◽  
Cell Types ◽  
Cellular Heterogeneity ◽  
Type I ◽  
Γδt Cells ◽  
Mait Cells ◽  
Integrative Analyses ◽  
Severe Infections

The mechanisms underlying the immune remodeling and severity response in coronavirus disease 2019 (COVID-19) are yet to be fully elucidated. Our comprehensive integrative analyses of single-cell RNA sequencing (scRNAseq) data from four published studies, in patients with mild/moderate and severe infections, indicate a robust expansion and mobilization of the innate immune response and highlight mechanisms by which low-density neutrophils and megakaryocytes play a crucial role in the cross talk between lymphoid and myeloid lineages. We also document a marked reduction of several lymphoid cell types, particularly natural killer cells, mucosal-associated invariant T (MAIT) cells, and gamma-delta T (γδT) cells, and a robust expansion and extensive heterogeneity within plasmablasts, especially in severe COVID-19 patients. We confirm the changes in cellular abundances for certain immune cell types within a new patient cohort. While the cellular heterogeneity in COVID-19 extends across cells in both lineages, we consistently observe certain subsets respond more potently to interferon type I (IFN-I) and display increased cellular abundances across the spectrum of severity, as compared with healthy subjects. However, we identify these expanded subsets to have a more muted response to IFN-I within severe disease compared to non-severe disease. Our analyses further highlight an increased aggregation potential of the myeloid subsets, particularly monocytes, in COVID-19. Finally, we provide detailed mechanistic insights into the interaction between lymphoid and myeloid lineages, which contributes to the multisystemic phenotype of COVID-19, distinguishing severe from non-severe responses.

scholarly journals Distribution of immune response cells in the pelvic urethra and the prepuce of rams

2014 ◽  
Vol 34 (3) ◽  
pp. 270-276 ◽  
Author(s):  
Jorge Acosta-Dibarrat ◽  
Alejandro Buendía-Jiménez ◽  
Edgardo Soriano-Vargas ◽  
Roberto Montes de Oca-Jiménez ◽  
Jorge Tórtora-Pérez
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Connective Tissue ◽  
Cell Types ◽  
Mucosal Immune Response ◽  
Image Analyzer ◽  
Mean Values ◽  
Accessory Glands ◽  
One Year ◽  
Number Of Cells

The pathogens of the reproductive system in the male can penetrate and establish by ascending route, from to the prepuce to the urethra, accessory glands, epididymis and testicles. The aim of this paper is determine the distribution and number of cells involved in the immune response in prepuce and pelvic urethra of rams, without apparent clinical alterations in testicle, epididymis and prepuce. The distribution of some of the cells involved in the immune response at the level of the prepuce and the pelvic urethra was quantified in four one-year-old rams seronegative for B. ovis and A. seminis and without apparent lesions in the testicles, the epididymis, and the prepuce. At the moment of slaughter, samples were taken from the preputial fornix and the pelvic urethra and placed in 10% formalin and under freezing conditions. CD4, CD8, WC1, CD45RO, CD14 and CD1b cells were demonstrated by immunohistochemistry, and immunoglobulin-containing cells (ICC) of the IgA, IgG and IgM classes were demonstrated by immunofluorescence. The labeled cells present in the mucosa of both organs were counted with an image analyzer. The total number of cells was compared between both tissues and differentially between the epithelium and the connective tissue of the mucosa. Significant differences were found in the total number of CD4, CD45RO, and WC1 lymphocytes, in CD14 macrophages, and CD1b dendritic cells, with mean values being greater in the fornix than in the urethra (p<0.05) in all cases. Only dendritic cells were found in the prepuce. No differences were found in the number of CD8 lymphocytes between both organs. The ratio between each cell type in the connective and the intraepithelial tissues and between organs was 10/1 for CD4 in the fornix (p<0.05), against 7/1 in the urethra (p<0.05), while CD8 had a 1/1 distribution in both mucosae. The WC1 ratio was 5/1 in both mucosae (p<0.05). CD45RO labeling was 19/1 in the prepuce (p<0.05) and 1/1 in the urethra. IgA-containing cells did not show differences in the total number of cells in both tissues. In the urethra, no IgG-containing cells were observed and IgM-containing cells were scarce; in contrast, both cell types were present in the prepuce, in amounts greater than in the urethra (p<0.05). IgA-, IgG-, and IgM-containing cells were located in both organs in the mucosal connective tissue. The presence of antigen-presenting cells, macrophages, and dendritic cells, as well as of lymphocytes CD4, CD8 TCR γδ (WC1), IgA-, IgG and IgM positive cells, and CD45RO cells suggests that both mucosae may behave as inductive and effector sites for the mucosal immune response.

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